Inhibins and activins were initially recognized as gonadal protein hormones which modulate follicle stimulating hormone (FSH) production.by the anterior pituitary gland. During the last grant period, these proteins have been characterized as alpha-beta-hetero- and beta-beta homodimers related to the TGF-0 family of growth and differentiation factors. Inhibin and activin subunits and their mRNA's are broadly distributed and have often mutually opposing actions on multiple tissues where they are hypothesized to play a variety of types of roles.as hormonal, paracrine and autocrine regulators of cellular function and proliferation. The aims of this project are to examine this hypothesis in the pituitary, placenta and brain. With improved immunologic and other tools, the chemical nature of the inhibin/activin-like proteins will be defined in those tissues shown to express inhibin/activin subunit mRNA's and the regulation of local production of inhibin and activin will be examined. The actions of exogenous inhibin and activin as well as neutralizing antibodies will be tested in vitro and in concert with other projects in vivo. Transgenic mice overexpressing the PA subunit and presumably activin will be developed and evaluated. The cellular actions of activin and inhibin along with the nature and regulation of the activin receptor will be explored. The proposed studies will improve our understanding of this new protein family and their roles in the regulation of reproduction.